This proposal has two major goals. First, to elucidate possible viral mechanisms of a SAIDS-associated neoplasm that is similar to KS in human AIDS; second, to study the effects of these viral mechanisms in vitro. Although KS is one of the most common neoplasms in AIDS patients, the role of HIV and immunosuppression in AIDS-associated KS is not understood. An appropriate animal model would furnish crucial information regarding the pathobiology of KS. Therefore, a nonhuman primate model of KS-like lesion, called RF, will be used for these studies. The morphology, immunophenotyic markers, and growth properties of RF and KS are very similar. RF is an aggressive and vascular proliferative disease associated with D-type simian retrovirus serotype 2 (SRV-2), an etiologic agent for SAIDS.
Specific aims are: (1) To investigate SRV-2-infected macaques with RF for possible coinfections with other viruses (e.g., EBV, CMV, STLV-1, HSV-1, HSV-2, and VZV); (2) To investigate the role of SRV-2 and coinfecting virus(es) in the induction of cytokines and/or growth factors in vitro and in vivo; (3) To determine the RF cell type associated with SRV-2 and the RF tumor. Clone and characterize RF cells, both with and without SRV-2 infection; (4) To investigate the transactivation of SRV-2 by coinfecting viruses; (5) To investigate the interactions between viral genes and gene products involved in the regulation of transcription of tumor growth factor genes. Protein extracts from RF tumor and cultured cells will be analyzed for binding to viral proteins; (6) To investigate the role of the viral genome in coding for neoplasm (RF); and (7) To test in vivo the hypotheses generated by in vitro studies of RF pathogenesis.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA054757-03
Application #
3199288
Study Section
Special Emphasis Panel (SRC (52))
Project Start
1991-03-15
Project End
1995-02-28
Budget Start
1993-03-01
Budget End
1994-02-28
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Other Domestic Higher Education
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195